Neisseria meningiditis is a leading cause of meningococcal disease and is endemic in many parts of the world. Polysaccharide (PS) vaccines for types A and C are effective in adults but not in infants. Covalently linking protein to the polysaccharide converts the antigen to one which is T cell dependent and is immunogenic in infants. We propose to synthesize protein- Ps conjugate vaccines for N. meningiditis A and C using novel chemistries to couple the protein to the Ps, either with or without a spacer, and over a wide range of protein to polysaccharide rations. Adult and neonatal nice will be immunized and antibody and bactericidal titers determined. We will evaluate whether the presence of unconjugated protein is detrimental or beneficial to the efficacy of the vaccine and whether it needs to be removed from the final vaccine preparation. The process of eliminating unconjugated protein from Ps-coupled protein as is currently done is expensive, reduces product yields and may be unnecessary. To test this, we will remove unconjugated protein using a proprietary and low cost method that we have developed. The chemistries and technology developed in this proposal can be applied to other protein-Ps conjugate vaccines and could result in significant savings. Proposed commercial applications: Neisseria meningiditis is a leading cause of meningococcal disease and is endemic and pandemic in certain arts of the world with consequent significant economic impact. Our proposed conjugate vaccines for types A and C would be less expensive to synthesize. They would be available for use in the developing world.